In this week's Nature, a multi-institute team of scientists describes the use of reverse genetics to determine the phenotypes of loss-of-function mutations, setting the stage for a "human knockout project" to understand the phenotypic consequences of complete disruption of genes. The researchers sequenced the gene-coding regions of more than 10,000 Pakistani individuals, identifying nearly 50,000 mutations predicted to cause loss of function in 1,317 genes. They then determined whether these changes were associated with any of about 200 traits measured in blood samples. In a proof-of-concept study, the scientists recruited individuals with a mutation linked to apolipoprotein C3 deficiency and demonstrated that this genetic feature was associated with an improved ability to clear dietary fat from circulation.
Also in Nature, an international group of investigators publishes an analysis of Ebola virus genomes, uncovering key factors involved in the recent epidemic in West Africa. The scientists looked at roughly 1,600 Ebola genomes, representing over 5 percent of known cases, and tested the association of geography, climate, and demography with viral movement. They discuss why the epidemic was limited to certain countries and show that the epidemic was "a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration, and connectivity." GenomeWen has more on this study, here.